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Abstract

The microcirculatory changes caused by hypercholesterolemia were studied in the rat cremaster muscle model by intravital microscopy and were compared with aortic ring segments from the same animals. Male Sprague-Dawley rats were fed either a normal chow diet or a chow diet supplemented with 1% cholesterol and 0.5% cholic acid for 3 or 5 weeks before experimentation. Three weeks of hypercholesterolemia produced a significantly decreased vasodilator response to serotonin in the arterioles. This response was also seen after 5 weeks on the hypercholesterolemia diet. Three weeks of hypercholesterolemia produced a significantly increased macromolecular leakage from postcapillary venules in response to serotonin. However, after 5 weeks of hypercholesterolemia, the serotonin-induced leakage was less than in control animals. Hypercholesterolemia for 3 weeks decreased the arteriolar dilation evoked by acetylcholine but did not change the arteriolar response to sodium nitroprusside. Contraction of the aortic rings induced by serotonin and aortic ring relaxation induced by sodium nitroprusside were not different between 3-week-control and 3-week-hypercholesterolemic animals. However, 3 weeks of hypercholesterolemia attenuated the aortic ring relaxation evoked by acetylcholine. These results suggest that hypercholesterolemia causes an early depression of endothelium-derived relaxing factor (EDRF)-mediated receptor responses in both microvessels and the aorta, whereas non-EDRF-mediated receptor responses are altered in the microcirculation but not in the aorta.